LncRNA landscape and associated ceRNA network in placental villus of unexplained recurrent spontaneous abortion.

BACKGROUND: Unexplained recurrent spontaneous abortion (URSA) is one of the most challenging conditions frustrates women of childbearing age profoundly. The gene expression patterns and biological characteristics of placental villus in patients with URSA remain largely unknown. The aim of our study was to identify potential lncRNAs as well as their action mechanisms in URSA. METHOD: The ceRNA microarray was used to identify the mRNA and lncRNA expression profiles of URSA patients and normal pregnancy. Functional enrichment analyses for differentially expressed mRNAs in URSA were performed. Protein-protein interaction analysis of differentially expressed mRNAs was performed to identify hub genes and key modules. Subsequently, the co-dysregulated ceRNA network of URSA was established, and the enrichment analyses for the mRNAs in the ceRNA network was implemented. qRT-PCR was performed to validated the expression of key ENST00000429019 and mRNAs in URSA. RESULTS: We found that URSA placental villus have distinct mRNA and lncRNA expression profiles through ceRNA microarray, with a total of 347 mRNAs and 361 lncRNAs differentially expressed compared with controls. The functional enrichment analysis revealed that ncRNA processing, DNA replication, cell cycle, apoptosis, cytokine-mediated signaling pathway, ECM-receptor interaction were the potentially disrupted pathways in URSA patients. Then we constructed a co-dysregulated ceRNA network and found differentially expressed mRNAs were regulated by a small fraction of hub lncRNAs. Finally, we found a key network of ENST00000429019 and three cell proliferation or apoptosis related key mRNAs (CDCA3, KIFC1, NCAPH), and validated their expression and regulation in tissue and cellular levels. CONCLUSIONS: This study identified a key ceRNA network, which might take part in URSA and correlate with cell proliferation and apoptosis. Optimistically, this study may deepen our apprehensions about the underlying molecular and biological causes of URSA and provide an important theoretical basis for future therapeutic strategies for patients with URSA.

Optical planar and ridge waveguides formed in Er3+-doped germanate glass by ion implantation and precise diamond blade dicing.

In this work, we report on the preparation and characterization of the planar and ridge optical waveguides in the Er3+-doped germanate glass by combining hydrogen ion implantation and precise diamond blade dicing. The nuclear energy loss and the implantation depth were calculated by the SRIM 2013 software. The refractive index profile was obtained by the reflectivity calculation method. The dark-mode spectrum and the near-field intensity distribution were measured by the prism coupling system and end-face coupling technique, respectively. This work has important reference significance for the development of Er3+-doped germanate glass active devices in the optical communication field.

Emergent complication of assisted reproductive technology: Clinical analysis of 17 pregnant women with adnexal torsion.

BACKGROUND: The purpose of this study was to evaluate the clinical symptoms, surgical management, and outcomes of pregnant women with adnexal torsion due to assisted reproductive technology. METHODS: It was a retrospective study that include 17 pregnant women with adnexal torsion, in which the maternal age, type of fertilization, gestational age, clinical symptoms, ultrasonic findings, side affected by the disease, surgical method, and pregnancy outcomes were evaluated. RESULTS: A total of 17 patients with adnexal torsion were included in this study, of which 8 patients conceived by in vitro fertilization-embryo transfer (IVF-ET), 1 by artificial insemination (AIH), and the other 8 conceived naturally after ovulation induction. About 14 were reported to have occurred in the first trimester of pregnancy, 1 case in the second trimester, and the other 2 in the third trimester. Clinical symptoms were abdominal pain with or without nausea and vomiting. 14 cases occurred in the right adnexa and the other 3 in the left. 5 of the patients underwent laparoscopy, and the other 12 underwent laparotomy. 8 cases were of full- term delivery, 6 twins gave birth prematurely, and 3 patients had inevitable abortion. CONCLUSIONS: Adnexal torsion is an acute onset of lower abdominal pain in women, which seldom occurs during pregnancy. However, because of the wide application of assisted reproductive technology (ART), its incidence has increased. Early diagnosis and treatment can lead to better results.

[Studies on dosage-efficacy/toxicity relationship of anti-hypoxia effects and quality standard of Tibetan medicine Brassicea Radix extract].

To evaluate the efficacy and safety associated with anti-hypoxia effect and establish the quality standard for Brassicea Radix extract, the investigations of acute toxicity and subacute toxicity were carried out to preliminarily appraise the toxicity, and the models of normal pressure hypoxia, acute cerebral ischemia and sodium nitrite poisoning in mice were used to evaluate the effect of enhancing anoxia endurance. Then according to the methods described in the Appendix of Chinese Pharmacopoeia (2010 edition), the sulfuric acid-phenol method was applied to determine the content of polysaccharide, and the water, ash and insoluble matter in water inspections were carried out and the control medicinal herb was identified with the samples by qualitative TLC. The results indicated that ① the toxic effects (LD50) of mice was 56.73 g•kg⁻¹ by oral administration of Brassicea Radix extract, while Dm and Dn were respective 86.80 g•kg•d⁻¹ and 35.55 g•kg•d⁻¹;②the determined effective dosage of Brassicea Radix extract which could enhance anoxia endurance was 0.388 g•kg⁻¹â€¢d⁻¹; ③ the methods of TLC and the content of polysaccharide were established. The method of quality control has been recorded in Sichuan Province Standard for Tibetan Medicine, which is reliable, accurate and simple, with good reproducibility. Meanwhile, given the prominent effect on anti-hypoxia and good safety, it provided important basis for clinic safe and effective usage and the development of health products.

[The state of HCV infection and vertical transmission during assisted reproductive technology].

Vertical transmission is the major route of HCV infection in children and draws much attention recently. With the development of assisted reproductive technology (ART), more and more HCV-serodiscordant infertile couples seek assisted reproduction treatment. Vertical transmission of HCV in ART cannot be avoided. Understanding the state of HCV infection of oocyte and embryo is helpful to solve the fertility problem and to control mother-to-child transmission.

[HPLC fingerprint of Tibetan medicine Shaji Gao].

This study established an HPLC fingerprint of Tibetan medicine Shaji Gao from different habitats and lay a foundation for Shaji Gao varieties identification and preparation process. The chromatographic condition was as follow: Agilent zorbax SB-C18 (4.6 mm x 250 mm, 5 µm) eluted with the mobile phases of acetonitrile and 0.4% phosphoric acid water in gradient mode. The flow rate was 1.0 mL x min(-1), and the detection wavelength was set at 360 nm. The fingerprints of 15 batches Shaji Gao were carried out by similarity comparation, 7 chromatographic peaks were extracted as the common peaks of fingerprint, 3 peaks were identified, which were quercetin, kaempferol and isorhamnetin. The similarity degrees of 14 batches of samples were above 0.9 and 1 batch of samples was below 0.9. This is the first established fingerprint of Shaji Gao by using HPLC. This method has good precision, stability and repeatability that it could provide basis for quality control and evaluation of Shaji Gao.

[Study on three different species tibetan medicine sea buckthorn by 1H-NMR-based metabonomics].

The 1H-NMR fingerprints of three different species tibetan medicine sea buckthorn were established by 1H-HMR metabolomics to find out different motablism which could provide a new method for the quality evaluation of sea buckthorn. The obtained free induction decay (FID) signal will be imported into MestReNova software and into divide segments. The data will be normalized and processed by principal component analysis and.partial least squares discriminant analysis to perform pattern recognition. The results showed that 25 metabolites belonging to different chemical types were detected from sea buckthorn,including flavonoids, triterpenoids, amino acids, carbohydrates, fatty acids, etc. PCA and PLS-DA analysis showed three different varietiest of sea buckthorn that can be clearly separated by the content of L-quebrachitol, malic acid and some unidentified sugars, which can be used as the differences metabolites of three species of sea buckthorn. 1H-NMR-based metabonomies method had a holistic characteristic with sample preparation and handling. The results of this study can offer an important reference for the species identification and quality control of sea buckthorn.

LSVC: A Lifelong Learning Approach for Stream-View Clustering.

Multiview clustering (MVC) can achieve more accurate results by utilizing complementary information from multiple perspectives, compared to traditional single-view methods. However, current multiview techniques require all views to be available upfront, making them inadequate for dealing with prevalent data sources that arrive as streams, such as stem cell analysis and multicamera surveillance. To address this problem, in this article, we propose a method called lifelong stream-view clustering (LSVC), which comprises an embedding anchor knowledge library and three key components, enabling the capability to perform asynchronous clustering on stream views. These three components are specifically: 1) the knowledge extraction module that extracts the abstract knowledge of the newcome view over time and updates the shared knowledge library; 2) the knowledge transfer module that aligns the newcome view with the historical knowledge library, enabling the transfer of structure information to the knowledge library; and 3) the knowledge rule module that constraints the knowledge library to enjoy a fair amount of anchors for each cluster, improving the discrimination of knowledge. The experimental results show that LSVC outperforms traditional single-view clustering (SVC) and MVC methods as it gradually improves with the accumulation of stream views and tends to be stable over time.

The risk of asthma in singletons conceived by ART: a retrospective cohort study.

STUDY QUESTION: Do singleton children conceived by ART have a higher asthma risk than naturally conceived (NC) singletons? SUMMARY ANSWER: The asthma risk was similar for ART-conceived singletons and NC singletons, and there were no clear differences between the various types of ART. WHAT IS KNOWN ALREADY: Whether ART increases asthma risk in offspring is questionable. The evidence is inconsistent and limited by ethnicity, geographic distribution, inadequate confounder adjustment, unsatisfactory control groups, and specific methods of ART. Furthermore, the mediating effects of obstetric and neonatal outcomes on the association between ART and asthma remain unclear. STUDY DESIGN SIZE DURATION: This observational, single-centre study was conducted at a reproductive centre of an affiliated university hospital between September 2009 and April 2023. A total of 3227 singletons aged 3-6 years conceived by IVF versus ICSI or fresh versus frozen embryo transfer were retrospectively enrolled, and a total of 1206 NC singletons of the same age were subsequently recruited. PARTICIPANTS/MATERIALS SETTING METHODS: Asthma was defined as a self-reported physician diagnosis or wheezing in the past 12 months. We performed multivariable logistic regression analyses to examine associations between asthma in offspring and ART use, adjusting for parental characteristics (age, education level, occupation type, BMI, asthma), smoking exposure, residence type, child sex, child age, and year of follow-up. Mediating effects were explored using longitudinal mediation structural equation modelling. MAIN RESULTS AND THE ROLE OF CHANCE: Asthma was reported for 51 (4.2%) of the 1206 NC singletons (median [interquartile range] age 5 [4-5] years; 48.1% females) and 169 (5.2%) of the 3227 ART-conceived singletons (5 [5-5] years; 47.6% females). We found that risks of childhood asthma in singletons conceived by ART were, overall, similar to those of NC singletons before (odds ratio [OR], 1.25 [95% CI, 0.92-1.74]; P = 0.170) and after adjustment (adjusted OR [aOR], 0.66 [95% CI, 0.44-1.03]; P = 0.126). The results were similar in multiple sensitivity analyses, and there were no clear differences in asthma risks according to the method of ART. Mediation analysis revealed a significant positive indirect effect of neonatal intensive care unit (NICU) admission (standard path coefficient, b = 0.025, P < 0.05) and a negative indirect effect of breastfeeding (b = -0.012, P < 0.05) on the association between ART and asthma in singleton offspring. LIMITATIONS REASONS FOR CAUTION: This study is limited to singletons only and cannot be generalized. The study is also limited by its retrospective observational single-centre nature and sample size. Mediation analyses were exploratory. Therefore, the findings need to be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: These findings can help infertile couples undergoing ART be reassured about the risk of childhood asthma in singleton offspring. Breastfeeding is recommended as a potentially feasible intervention to reduce the asthma risks in ART-conceived children who are at increased potential risk of asthma, such as those with NICU admissions. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the Key Research and Development Program of Zhejiang Province (2021C03100), the National Key Research and Development Program of China (2021YFC2700603), and the Program for Key Subjects of Zhejiang Province in Medicine and Hygiene to Y. Z., the Zhejiang Province Natural Science Foundation (No. LQ22H040006) and the National Natural Science Foundation of China (No.82101759) to M.T., and the National Natural Science Foundation of China (No. 82201860) to J.Y. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: ChiCTR2300069906.

[Analysis and thinking on status of quality standard of ethnic medicine].

The establishing and improving of quality standards for ethnic medicine have close relation with the safety and efficacy of clinical medicine. It is significant to promote the modernization and industrialization of ethnic medicine. This paper summarized the present status of quality standards for ethnic medicine, and pointed out the deficiency of ethnic medicine; the origin of medicinal materials was not clear and varieties were confused; the safety research of mineral drug was weak and so on. Based on these, firstly, the research of quality standards for ethnic medicine should be under the guidance of ethnic traditional medical theory and clinical experience and strengthen the quality control and evaluation of safety and effectiveness for ethnic medicine. Further, much attention should be payed to protection of natural medicinal resources and sustainable utilization. Lastly, modern chemical analysis technology shouled be used during the research process on the basis of ethnic characteristics. It will promote the establishment and improvement of quality standards for ethnic medicine and will be benificial to modernization and industrialization development of ethnic medicine.

One-Stage Shifted Laplacian Refining for Multiple Kernel Clustering.

Graph learning can effectively characterize the similarity structure of sample pairs, hence multiple kernel clustering based on graph learning (MKC-GL) achieves promising results on nonlinear clustering tasks. However, previous methods confine to a "three-stage" scheme, that is, affinity graph learning, Laplacian construction, and clustering indicator extracting, which results in the information distortion in the step alternating. Meanwhile, the energy of Laplacian reconstruction and the necessary cluster information cannot be preserved simultaneously. To address these problems, we propose a one-stage shifted Laplacian refining (OSLR) method for multiple kernel clustering (MKC), where using the "one-stage" scheme focuses on Laplacian learning rather than traditional graph learning. Concretely, our method treats each kernel matrix as an affinity graph rather than ordinary data and constructs its corresponding Laplacian matrix in advance. Compared to the traditional Laplacian methods, we transform each Laplacian to an approximately shifted Laplacian (ASL) for refining a consensus Laplacian. Then, we project the consensus Laplacian onto a Fantope space to ensure that reconstruction information and clustering information concentrate on larger eigenvalues. Theoretically, our OSLR reduces the memory complexity and computation complexity to O(n) and O(n2) , respectively. Moreover, experimental results have shown that it outperforms state-of-the-art MKC methods on multiple benchmark datasets.

Health poverty alleviation in China from the perspective of historical institutionalism: policy changes and driving factors.

Health poverty alleviation is an effective tool for improving the living quality and developmental conditions of impoverished populations. Since 1978, China has been actively implementing health poverty alleviation projects, resulting in a more robust rural healthcare service network and increased convenience for the local population to access medical treatment. However, it is crucial to acknowledge that China still faces a complex situation with the simultaneous existence of multiple disease threats and the interweaving of various health influencing factors. Ongoing risks of emerging infectious diseases persist, and some previously controlled or eliminated infectious diseases are at risk of resurgence. The incidence of chronic diseases is on the rise and exhibits a trend toward affecting younger populations. Therefore, examining the successful experiences of China's health poverty alleviation over the past 40 years becomes a critically important issue. The study focuses on China's health poverty alleviation policies, employing historical institutionalism as a theoretical perspective to analyze the historical changes and evolutionary logic of health poverty alleviation policies. A historical institutionalist analytical framework for health poverty alleviation policies is constructed. The research findings reveal that China's health poverty alleviation policy has undergone three distinct periods since 1978: the initial phase (1978-2000), the exploratory phase (2000-2012), and the stable development phase (2013-present). At the macro level, the political, economic, and social contexts of different periods have influenced the evolution of health poverty alleviation policies. On the meso level, coordination effects and adaptive expectations have had an impact on China's health poverty alleviation policy. At the micro level, various actors, including the central government, local governments at different levels, social forces, and impoverished communities, interact during the evolution of health poverty alleviation policies. This paper summarizes the theoretical aspects of China's health poverty alleviation policy experience. The research conclusions, viewed through the lens of historical institutionalism, offer practical insights into the evolution of government policies. This provides directional guidance for enhancing health poverty alleviation projects.

circRNA-DURSA regulates trophoblast apoptosis via miR-760-HIST1H2BE axis in unexplained recurrent spontaneous abortion.

Unexplained recurrent spontaneous abortion (URSA) is one of the most intractable clinical challenges in reproduction. As a specific type of endogenous non-coding RNA, circular RNAs (circRNAs) have great pre-clinical diagnostic and therapeutic values in diseases. Recently, thousands of circRNAs were detected in human pre-implantation embryos, indicating that circRNAs potentially have important regulatory functions. However, the roles of circRNAs in URSA remain largely unknown. In this study, we elucidated deregulated circRNA expression and distinct competing endogenous RNA (ceRNA) networks by comparing URSA placental villus with that of patients with normal pregnancy using microarrays. We characterized a distinct circRNA, circRNA-0050703, which is downregulated in URSA placental villus (thus we named it circRNA-DURSA). Silencing of circRNA-DURSA results in trophoblast cell apoptosis in vitro. Furthermore, mechanistic dissection revealed that circRNA-DURSA exerts its effects by competitively binding to miR-760, which post-transcriptionally targets HIST1H2BE. Additionally, after circRNA-DURSA silencing in vivo, the numbers of implanted embryos decreased significantly. These results reveal the regulatory roles of circRNA-DURSA in trophoblasts and identified a distinct circRNA-DURSA/miR-760/HIST1H2BE axis as potentially important diagnostic and therapeutic targets for URSA treatment.

The BMP2 Signaling Axis Promotes Invasive Differentiation of Human Trophoblasts.

Embryo implantation and trophoblast invasion are principal limiting factors of pregnancy establishment. Aberrant embryo development or improper trophoblast differentiation and invasion may lead to various unfavorable pregnancy-related outcomes, including early pregnancy loss (EPL). Our clinical data show that the serum BMP2 levels were significantly increased during the first trimester of pregnancy and that the serum and BMP2 expression levels were lower in women with EPL than in women with normal early pregnancies. Moreover, we observed that BMP2 was expressed in oocytes and trophoblast cells of cleaved embryos and blastocysts prior to implantation in both humans and mice. Exogenous BMP2 promoted embryonic development by enhancing blastocyst formation and hatching in mice. LncRNA NR026833.1 was upregulated by BMP2 and promoted SNAIL expression by competitively binding to miR-502-5p. SNAIL induced MMP2 expression and promoted cell invasion in primary extravillous trophoblast cells. BMP2 promotes the invasive differentiation of mouse trophoblast stem cells by downregulating the expression of TS cell marker and upregulating the expression of trophoblast giant cell marker and labyrinthine/spongiotrophoblast marker. Our findings provide significant insights into the regulatory roles of BMP2 in the development of the placenta, which may give us a framework to explore new therapeutic strategies to pregnancy-related complications.

Influence of cleavage-stage embryo quality on the in-vitro fertilization outcome after single embryo transfer in fresh cycles.

OBJECTIVE: Embryo quality is crucial for determining the outcome of embryo implantation. This study aimed to assess the impact of embryo quality on the outcome of in vitro fertilization/single-embryo transfer (IVF-SET). MATERIALS AND METHODS: This retrospective study included 2531 fresh IVF-SET cycles, including 277 poor-quality and 2254 top-quality embryos. The clinical pregnancy rate, miscarriage rate, live birth, implantation rate, pregnancy outcome and complication were analyzed and compared. Risk factors associated with miscarriage rate and pregnancy complication were identified using logistics regression analysis. RESULTS: Top-quality embryos resulted in higher clinical pregnancy rate (30.5% vs. 12.6%, P < 0.001) and live birth rate (23.9% vs. 9.7%, P < 0.001) compared with poor-quality embryos. Logistics regression analysis revealed that embryo quality was not correlated with miscarriage rate (95% CI 0.33-1.89) and pregnancy complications (95% CI 0.12-7.84). Maternal age and body mass index was a risk factor for miscarriage rate (95% CI 1.05-1.22) and pregnancy complication (95% CI 1.01-1.29), respectively. CONCLUSION: Clinical miscarriage rate and pregnancy complication were embryo quality independent. Maternal age was the risk factor for miscarriage rate. Embryo quality did not affect miscarriage once a clinical pregnancy is achieved.

Impact of Galectin-1 on Trophoblast Stem Cell Differentiation and Invasion in In Vitro Implantation Model.

Trophoblast stem cells (TSCs) differentiate in an orderly manner, which plays an important role in the process of embryo implantation, placentation, and early pregnancy maintenance. At the maternal-fetal interface, the dialogue is crucial between trophoblast cells and endometrial epithelial cells. Previous studies suggested that galectin-1 (Gal-1) may play an important role in placental development. In this study, we used Ishikawa (IK) cells-TSC coculture model to simulate the maternal-fetal interface and induce the differentiation of TSCs by differentiation media. The messenger RNA level of each cell type markers, fusion markers, and Gal-1 was detected by quantitative reverse transcription polymerase chain reaction during the differentiation of TSCs. Wound healing and transwell invasion assays were used to detect the migration and invasion ability in each group. We found that coculture with IK cells or conditioned media from IK cells could promote the differentiation and invasion of TSCs and increase Gal-1 expression in TSCs. Furthermore, recombinant Gal-1 could also promote the differentiation and invasion of TSCs, suggesting that some of IK cells secretion increase the expression of Gal-1 in TSCs during implantation, which then induced trophoblast differentiation and invasion in vitro. These findings provide significant insights into the biology of embryo-maternal interactions with the importance of Gal-1 in TSCs for the successful establishment and maintenance of pregnancy.

A potential role of galectin-1 in promoting mouse trophoblast stem cell differentiation.

Galectin-1 is highly expressed in blastocysts and trophoblast giant cells during implantation, and dysregulated galectin-1 is associated with many pregnancy-related abnormalities. Elevated galectin-1 contributes to cancer cells invasion. Here, we found that galectin-1 is expressed in mouse oocytes, preimplantation embryos (all stages), and trophoblast stem (TS) cells. Peak levels of galectin-1 mRNA and protein were detected on day 4 and day 5 after the induction of TS cells differentiation. Overexpression of galectin-1 increased TS cells migration and invasion, whereas knockdown of galectin-1 attenuated these effects. Additionally, knockdown of galectin-1 in TS cells decreased the expression of matrix metalloproteinase (MMP) 2/9, ZEB-1, Snail, N-cadherin, TGF-ß, Nodal, and phospho-Smad2/3, whereas the expression of E-cadherin was increased. In contrast, overexpression of galectin-1 in TS cells increased the expression of MMP2/9, ZEB-1, and N-cadherin, whereas the expression of E-cadherin was decreased. These findings suggest a potential role of galectin-1 in the differentiation of mouse TS cells.

A Model of Regularization Parameter Determination in Low-Dose X-Ray CT Reconstruction Based on Dictionary Learning.

In recent years, X-ray computed tomography (CT) is becoming widely used to reveal patient's anatomical information. However, the side effect of radiation, relating to genetic or cancerous diseases, has caused great public concern. The problem is how to minimize radiation dose significantly while maintaining image quality. As a practical application of compressed sensing theory, one category of methods takes total variation (TV) minimization as the sparse constraint, which makes it possible and effective to get a reconstruction image of high quality in the undersampling situation. On the other hand, a preliminary attempt of low-dose CT reconstruction based on dictionary learning seems to be another effective choice. But some critical parameters, such as the regularization parameter, cannot be determined by detecting datasets. In this paper, we propose a reweighted objective function that contributes to a numerical calculation model of the regularization parameter. A number of experiments demonstrate that this strategy performs well with better reconstruction images and saving of a large amount of time.

Dendrimeric anticancer prodrugs for targeted delivery of ursolic acid to folate receptor-expressing cancer cells: synthesis and biological evaluation.

The anticancer efficacy of ursolic acid (UA) was limited by poor water solubility, non-specific tumor distribution, and low bioavailability. To overcome this problem, polyamidoamine (PAMAM) conjugated with UA and folic acid (FA) as novel dendrimeric prodrugs were designed and successfully synthesized by a concise one-pot synthetic approach. Both FA and UA were covalently conjugated to the surface of PAMAM through acid-labile ester bonds and the covalently linked UA could be hydrolysed either in acidic (pH 5.4) or in neutral (pH 7.4) PBS solution. The cellular uptake study indicated that the presence of FA enhanced uptake of the dendrimeric prodrugs in folate receptor (FR) over-expressing Hela cells. The enhanced cellular uptake could be due to the electrostatic absorptive endocytosis and FR-mediated endocytosis. In contrast, for HepG2 cells, a FR-negative cell line, FA conjugation on the surface of the dendrimer showed no effect on the cellular uptake. In MTT assay and cell cycle analysis, FA-modified dendrimeric prodrugs showed significantly enhanced toxicity than non-FA-modified ones in Hela cells. These results suggested that FA-modified dendrimeric UA prodrugs have the potential for targeted delivery of UA into cancer cells to improve its anti-tumor efficacy.